先天性巨細胞病毒感染對於兒童聽損之影響：初報 羅大烜 吳振吉 許巍鐘 呂俊毅 劉殿楨 許權振 台大醫院耳鼻喉部

Introduction Sensorineural hearing loss (SNHL) is the most common sensory defect in children Among non-genetic causes of SNHL, congenital cytomegalovirus (cCMV) infection is the most prevalent1,2 cCMV infection accounts for 10-20% SNHL in children1,2

Congenital CMV infection (0.58-0.7% in industrialized contries) 2-4 ~1/10 ~9/10 Symptomatic Neonates Asymptomatic Neonates • IUGR • Microcephaly • Petechiae • Hepatosplenomegaly • Encephalitis • CNS defect (ex. SNHL)

Congenital CMV infection (0.58-0.7% in industrialized contries) 2-4 ~1/10 ~9/10 Symptomatic Neonates Asymptomatic Neonates 40-50% 13.5% Sequelae Sequelae Hearing loss: most common Congenital or progressive Bilateral or unilateral Treatable w/ antiviral mx

Patients cCMV infection N=35 Asymptomatic at birth N= 16 Passed NHS (2014 ~, NTUH) Asymptomatic at birth N= 16 Passed NHS N=16 Failed NHS N=0 N=12 N=5 No NHS data N=2 Symptomatic at birth N= 19 NHS: New born hearing screen

Patients cCMV infection N=35 Asymptomatic at birth N= 16 Passed NHS (2014 ~, NTUH) Asymptomatic at birth N= 16 Passed NHS N=16 Failed NHS N=0 N=12 N=5 No NHS data N=2 Symptomatic at birth N= 19 NHS: New born hearing screen

Assessments CMV viral load Audiologic assessments Blood serum viral load (cp/ml) Initial viral load: viral load tested within 1 m after birth Viral suppression: serum viral load reduced to undetectable Audiologic assessments AABR, DPOAEs, ABR, sound field, PTA Grades of hearing loss5 26-40dB Mild 41-70dB Moderate 71-90dB Severe >91dB Profound

Demographic data Characteristics N (%) Total 35 Male 24 69% Female 11 31% Passed NHS 21 60% Failed NHS 12 34% No NHS data 2 6% Asymptomatic 16 46% Symptomatic 19 54% HL 15 43% Unilateral HL 7 20% Bilateral HL 8 23% No HL No Hearing test data 1 3%

NHS or neonatal symptoms as predictors? 100 (12/12) 83.3 (15/18) 9.5 (2/21) 0 (0/16) p < 0.01 p < 0.01

Unilateral vs. Bilateral HL Bilateral 較嚴重? => no P>0.05

Initial viral load vs. Hearing features Initial viral load vs. NHS Initial viral load vs. HL p = 0.09 p = 0.07 Pass NHS Fail NHS Initial VL (cp/ml) No HL HL Initial VL (cp/ml) Boxplot of Initial VL and for NHS and HL. Box, defined by quartiles Q1 and Q3; bar, median; whiskers, lowest and highest value; o, outliers

Viral suppression and HL Serum viral load decreased gradually in most patients Most patients achieved serum viral suppression before 1 y (median = 4.5 m) Most patients showed stable hearing levels as the viral load decreased Some exceptions Throat/Urine VL suppression date?

Special case -1 Hearing loss deteriorated even after the viral load reached undetectable level

Special case -2 A case with immunodeficiency (Activated PI3K-delta syndrome) Focus 在後面

Conclusions Failing NHS or being symptomatic at birth are predictors of HL development in cCMV infection Severity of hearing loss was not different between uni- and bilateral cases Initial viral load was not significantly related to NHS or hearing loss development Hearing deterioration could occur even in cases with serum viral suppression

Thanks for attention!!

Reference Morton CC, Nance WE. Newborn hearing screening—a silent revolution. N Engl J Med 2006;354:2151-64. Goderis J, De Leenheer E, et al. Hearing loss and congenital CMV infection: a systematic review. Pediatrics 2014;134:972-82. Dollard SC, Grosse SD, et al. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 2007;17:355-63. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus infection. Rev Med Virol 2007;17:253-76. Julie G., et al., Hearing in Children with Congenital Cytomegalovirus Infection:Results of a Longitudinal Study, J Pediatr 2016;172:110-5